crossing96/oncoscreening huggingface dataset:
Systematic review and meta-analysis of randomized controlled trials of perioperative outcomes and prognosis of transurethral en-bloc resection vs. conventional transurethral resection for non-muscle-invasive bladder cancer.	OBJECTIVES: This article aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) of perioperative outcomes and prognosis of transurethral en-bloc resection versus conventional transurethral resection for non-muscle-invasive bladder cancer (NMIBC). METHODS: We searched MEDLINE, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) to find eligible RCTs. The studies were classified by version 2 of the Cochrane risk-of-bias tool for randomized trials. Review Manager 5.4.0 was used to evaluate the data. The certainty of the evidence was assessed using the Guideline Development Tool by GRADEpro GDT. RESULTS: Seven RCTs with 1142 patients was included in the present study. The results indicated that bladder perforation (OR = 0.17; 95% CI 0.05 to 0.67; P = 0.01), obturator nerve reflex (OR = 0.03; 95% CI 0.01 to 0.13; P < 0.00001), residual tumor (OR = 0.24; 95% CI 0.08 to 0.77; P = 0.02) and repeat transurethral resection of bladder tumor (re-TURBT) (OR = 0.54; 95% CI 0.34 to 0.85; P = 0.008) were significantly reduced in the en-bloc resection group than the conventional resection group. However, there were no significant differences in hemoglobin deficit (p = 0.31), urethral stricture (p = 0.47), and detrusor muscle presence (P = 0.16) between both groups. Besides, resection time (p = 0.25), operative time (p = 0.20), catheter dwell time (p = 0.24), and length of hospital stay (p = 0.16) were similar in the two groups. Meanwhile, en-bloc resection yielded no advantage for the 3-month (P = 0.11), 6-month (P = 0.05), 1-year (P = 0.61), 2-year (P = 0.53), and 3-year (P = 0.26) tumor recurrence rates. CONCLUSIONS: Our meta-analysis shows that transurethral en-bloc resection is associated with comparable outcomes to conventional transurethral resection for recurrence-free survival in NMIBC patients. En-bloc resection is more feasible and safer than conventional resection for NMIBC, with fewer intraoperative complications, less residual tumor, and less re-TURBT.	bladder
Comparative performance of the different orthotopic urinary diversions.	PURPOSE OF REVIEW: Majority of patients undergoing radical cystectomy are suitable for orthotopic urinary diversion. The effect of different techniques of neobladder reconstruction on early and long-term postoperative complications is still being determined. Additionally, it is unclear which type of neobladder provides the best patient satisfaction. The purpose of this article is to review the outcomes of different orthotopic urinary diversions following radical cystectomy. RECENT FINDINGS: Ileal neobladder is the preferred type of orthotopic urinary diversion following radical cystectomy. Hautmann and Studer, which are the most common orthotopic diversion techniques, provide daytime continence rate up to 87% and 92%, respectively. However, nighttime continence is achieved in about 50% of patients. High-level evidence supports the long-term safety of orthotopic neobladder in terms of renal function, even in patients with a glomerular filtration rate <60 ml/min. Sexual dysfunction is the only independent factor associated with poorer quality of life in these patients. SUMMARY: The best type of neobladder is still uncertain. However, Studer and Hautmann are the most commonly performed techniques that provide favorable short- and long-term outcomes.	bladder
Progression-free survival is an adequate endpoint for clinical trials of locally advanced and metastatic urothelial carcinoma.	PURPOSE OF REVIEW: To evaluate intermediate clinical endpoints that have been proposed as potential surrogates for overall survival amongst patients with locally advanced and metastatic urothelial carcinoma. RECENT FINDINGS: Several endpoints have been proposed as potential surrogates for overall survival. They are: pathologic downstaging or complete response after neoadjuvant treatments and progression-free survival in the adjuvant setting and metastatic setting. Formal surrogacy, as per Prentice, has not been established among any of the aforementioned intermediate clinical endpoints and overall survival. Despite that, regulatory agencies have recently approved adjuvant nivolumab for patients with high-risk muscle invasive bladder cancer, based on the results of a trial that had disease-free survival as primary endpoint. SUMMARY: Despite the lack of proven surrogacy between progression-free survival and overall survival, this endpoint seems adequate for trial design and medication approval, as the recent case of adjuvant nivolumab demonstrates.	bladder
PAI-1 is a potential transcriptional silencer that supports bladder cancer cell activity.	The extracellular activity of Plasminogen activator inhibitor-1 (PAI-1) is well described, acting as an inhibitor of tissue plasminogen activator and urokinase-type plasminogen activator, impacting fibrinolysis. Recent studies have revealed a pro-tumorigenic role of PAI-1 in human cancers, via the regulation of angiogenesis and tumor cell survival. In this study, immunohistochemical staining of 939 human bladder cancer specimens showed that PAI-1 expression levels correlated with tumor grade, tumor stage and overall survival. The typical subcellular localization of PAI-1 is cytoplasmic, but in approximately a quarter of the cases, PAI-1 was observed to be localized to both the tumor cell cytoplasm and the nucleus. To investigate the potential function of nuclear PAI-1 in tumor biology we applied chromatin immunoprecipitation (ChIP)-sequencing, gene expression profiling, and rapid immunoprecipitation mass spectrometry to a pair of bladder cancer cell lines. ChIP-sequencing revealed that PAI-1 can bind DNA at distal intergenic regions, suggesting a role as a transcriptional coregulator. The downregulation of PAI-1 in bladder cancer cell lines caused the upregulation of numerous genes, and the integration of ChIP-sequence and RNA-sequence data identified 57 candidate genes subject to PAI-1 regulation. Taken together, the data suggest that nuclear PAI-1 can influence gene expression programs and support malignancy.	bladder
Association of artificial intelligence-powered and manual quantification of programmed death-ligand 1 (PD-L1) expression with outcomes in patients treated with nivolumab ± ipilimumab.	Assessment of programmed death ligand 1 (PD-L1) expression by immunohistochemistry (IHC) has emerged as an important predictive biomarker across multiple tumor types. However, manual quantitation of PD-L1 positivity can be difficult and leads to substantial inter-observer variability. Although the development of artificial intelligence (AI) algorithms may mitigate some of the challenges associated with manual assessment and improve the accuracy of PD-L1 expression scoring, use of AI-based approaches to oncology biomarker scoring and drug development has been sparse, primarily due to the lack of large-scale clinical validation studies across multiple cohorts and tumor types. We developed AI-powered algorithms to evaluate PD-L1 expression on tumor cells by IHC and compared it with manual IHC scoring in urothelial carcinoma, non-small cell lung cancer, melanoma, and squamous cell carcinoma of the head and neck (prospectively determined during the phase II and III CheckMate clinical trials). 1,746 slides were retrospectively analyzed, the largest investigation of digital pathology algorithms on clinical trial datasets performed to date. AI-powered quantification of PD-L1 expression on tumor cells identified more PD-L1-positive samples compared with manual scoring at cutoffs of ≥1% and ≥5% in most tumor types. Additionally, similar improvements in response and survival were observed in patients identified as PD-L1-positive compared with PD-L1-negative using both AI-powered and manual methods, while improved associations with survival were observed in patients with certain tumor types identified as PD-L1-positive using AI-powered scoring only. Our study demonstrates the potential for implementation of digital pathology-based methods in future clinical practice to identify more patients who would benefit from treatment with immuno-oncology therapy compared with current guidelines using manual assessment.	bladder
CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study.	This study explored the role of cancer susceptibility 1 (CASC1) in tumorigenesis and development as well as the key pathways affecting bladder cancer progression. CASC1 was examined in various normal tissues in humans using the HPA database to quantify its expression level and subcellular localization. CASC1 is abundantly expressed in tumor tissues, primarily in cytoplasmic vesicles and stroma. TIMER2 was used to analyze the correlation between CASC1 expression levels and the types of infiltrates associated with immune cells and immunosuppressive cells. MDSC, Treg, M2, and CAF were significantly correlated with CASC1 expression in various tumors. Comparing patients with and without CASC1 mutation, those with CASC1 mutation had worse overall survival, progression-free survival, and disease-free survival. The correlation between has-miR-150 and CASC1 (for the case of bladder cancer) was then analyzed, and the related ceRNA network was mapped. A negative relationship between CASC1 expression and has-miR-150 expression was found in cases of bladder cancer. And the presence of miR-150-targeted CASC1 may be associated with bladder cancer progression. CASC1 is expressed at elevated levels in various tumor tissues, and it is associated with tumorigenesis and development. Exosomes containing miR-150-targeted CASC1 may affect the progression of bladder cancer.	bladder
Allosteric activation of the metabolic enzyme GPD1 inhibits bladder cancer growth via the lysoPC-PAFR-TRPV2 axis.	BACKGROUND: Bladder cancer is the most common malignant tumor of the urinary system. Surgical resection and chemotherapy are the two mainstream treatments for bladder cancer. However, the outcomes are not satisfactory for patients with advanced bladder cancer. There is a need to further explore more effective targeted therapeutic strategies. METHODS: Proteomics were performed to compare protein expression differences between human bladder cancer tissues and adjacent normal tissues. The function of GPD1 on bladder cancer cells were confirmed through in vivo and in vitro assays. Transcriptomics and metabolomics were performed to reveal the underlying mechanisms of GPD1. Virtual screening was used to identify allosteric activator of GPD1. RESULTS: Here, we used proteomics to find that GPD1 expression was at low levels in bladder cancer tissues. Further investigation showed that GPD1 overexpression significantly promoted apoptosis in bladder cancer cells. Based on transcriptomics and metabolomics, GPD1 promotes Ca(2+) influx and apoptosis of tumor cells via the lysoPC-PAFR-TRPV2 axis. Finally, we performed a virtual screening to obtain the GPD1 allosteric activator wedelolactone and demonstrated its ability to inhibit bladder tumor growth in vitro and in vivo. CONCLUSIONS: This study suggests that GPD1 may act as a novel tumor suppressor in bladder cancer. Pharmacological activation of GPD1 is a potential therapeutic approach for bladder cancer.	bladder
Inherited Germline Cancer Susceptibility Gene Variants in Individuals with Non-Muscle-Invasive Bladder Cancer.	PURPOSE: Identification of inherited germline variants can guide personalized cancer screening, prevention, and treatment. Pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes are frequent among patients with locally advanced or metastatic urothelial carcinoma, but their prevalence and significance in patients with non-muscle-invasive bladder cancer (NMIBC), the most common form of urothelial carcinoma, is understudied. EXPERIMENTAL DESIGN: Germline analysis was conducted on paired tumor/normal sequencing results from two distinct cohorts of patients initially diagnosed with NMIBC. Associations between clinicopathologic features and clinical outcomes with the presence of P/LP germline variants in ≥76 hereditary cancer predisposition genes were analyzed. RESULTS: A similar frequency of P/LP germline variants were seen in our two NMIBC cohorts [12% (12/99) vs. 8.7% (10/115), P = 0.4]. In the combined analysis, P/LP germline variants were found only in patients with high-grade NMIBC (22/163), but none of the 46 patients with low-grade NMIBC (13.5% vs. 0%, P = 0.005). Fifteen (9.2%) patients with high-grade NMIBC had P/LP variants in DNA damage response genes, most within the nucleotide excision repair (ERCC2/3) and homologous recombination repair (BRCA1, NBN, RAD50) pathways. Contrary to prior reports in patients with NMIBC not receiving Bacillus Calmette-Guerin (BCG), P/LP germline variants were not associated with worse recurrence-free or progression-free survival in patients treated with BCG or with risk of developing upper tract urothelial carcinoma. CONCLUSIONS: Our results support offering germline counseling and testing for all patients with high-grade bladder cancer, regardless of initial tumor stage. Therapeutic strategies that target impaired DNA repair may benefit patients with high-grade NMIBC.	bladder
Comparative analysis of three vs. four cycles of neoadjuvant gemcitabine and cisplatin for muscle invasive bladder cancer.	PURPOSE: Because the optimal number of cycles of neoadjuvant gemcitabine and cisplatin chemotherapy (GC) is unclear, we aimed to compare disease response and survival outcomes of patients receiving either 3 or 4 cycles of neoadjuvant GC for muscle-invasive bladder cancer (MIBC). METHODS: A total of 166 patients who were treated with neoadjuvant GC and radical cystectomy for clinical stage T2-4N0M0 were identified. Response and effectiveness of different cycle counts were assessed using downstaging (complete pathologic and partial pathologic response), cancer-specific survival (CSS), and overall survival (OS). Response and survival outcomes were examined with adjusted logistic regression and Cox regression models. Statistical significance was defined as P < 0.05. RESULTS: Of 166 patients who received neoadjuvant GC, 107 (64.5%) received 3 cycles and 59 (35.5%) received 4 cycles. Age, insurance, comorbidity, tumor histology (pure urothelial carcinoma, urothelial with divergent differentiation, variant histology), and tumor stage were similar between the 2 treatment groups. Rates of complete response or any downstaging were similar between groups (21.5% and 40.2% in the 3-cycle group and 20.3% and 44.1% in the 4-cycle group, respectively). While disease response was similar (OR 1.03, 95% CI 0.43-2.45), both cancer-specific survival (HR 1.69, 95% CI 0.87-3.26) and overall survival (HR:1.88, 95% CI:1.02-3.48) were more favorable among patients managed with 4 cycles of neoadjuvant chemotherapy compared to those who received 3 cycles in adjusted models. CONCLUSIONS: Our analysis demonstrated that survival outcomes tended to be better among patients who received 4 cycle of neoadjuvant GC compared to those treated with 3 cycles. Although potential benefits of omission of fourth cycle may include expedited time to surgery, reduced chemotherapy-associated toxicity, and lower treatment costs, continuation of treatment with a fourth cycle of neoadjuvant GC chemotherapy may benefit patients with muscle-invasive bladder cancer and further improve disease outcomes.	bladder
LINC00702-mediated DUSP1 transcription in the prevention of bladder cancer progression: Implications in cancer cell proliferation and tumor inflammatory microenvironment.	BACKGROUND: Long noncoding RNAs (lncRNAs) can mediate the biological processes during tumorigenesis which may be affected by tumor associated macrophages (TAMs). Hence, we aim to identify the functionality of LINC00702 in regulation of bladder cancer cells and M2-TAMs. METHODS: After induction of M2-TAMs from THP-1 monocyte, we evaluated effects of LINC00702 on bladder cancer cells and M2-TAMs, which were validated in a xenograft tumor mouse model. RESULTS: Low LINC00702 expression was determined in bladder cancer tissues. LINC00702 could promote DUSP1 transcription by recruiting JUND to its promoter. Ectopic LINC00702 expression suppressed the bladder cancer cell proliferation and secretion of inflammatory cytokines by M2-TAMs through up-regulation of DUSP1. The anti-tumor activity of LINC00702 was ultimately validated in vivo. CONCLUSION: LINC00702 promoted DUSP1 by recruiting JUND to inhibit the proliferation of bladder cancer cells and the secretion of inflammatory factors, thus modulating bladder cancer inflammatory microenvironment.	bladder
Computational Analysis Identifies Novel Biomarkers for High-Risk Bladder Cancer Patients.	In the case of bladder cancer, carcinoma in situ (CIS) is known to have poor diagnosis. However, there are not enough studies that examine the biomarkers relevant to CIS development. Omics experiments generate data with tens of thousands of descriptive variables, e.g., gene expression levels. Often, many of these descriptive variables are identified as somehow relevant, resulting in hundreds or thousands of relevant variables for building models or for further data analysis. We analyze one such dataset describing patients with bladder cancer, mostly non-muscle-invasive (NMIBC), and propose a novel approach to feature selection. This approach returns high-quality features for prediction and yet allows interpretability as well as a certain level of insight into the analyzed data. As a result, we obtain a small set of seven of the most-useful biomarkers for diagnostics. They can also be used to build tests that avoid the costly and time-consuming existing methods. We summarize the current biological knowledge of the chosen biomarkers and contrast it with our findings.	bladder
Magnetic multi-enzyme cascade combined with liquid chromatography tandem mass spectrometry for fast DNA digestion and quantitative analysis of 5-hydroxymethylcytosine in genome of human bladder cancer T24 cells induced by tetrachlorobenzoquinone.	Long-term exposure to halobenzoquinones (HBQs) can induce genomic damages and abnormal epigenetic modifications. High-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) has shown unique advantages in identification and sensitive analysis of these structurally modified DNA lesions. Prior to MS analysis, genomic DNA needs to be fully digested into mono-nucleosides. Here, we prepared Supernuclease (SN)-, snake venom phosphodiesterase (SVP)- and calf intestinal alkaline phosphatase (CIP)- individually immobilized magnetic nanoparticles (MNPs), and combined them according to certain formula to construct a recyclable SN-SVP-CIP magnetic nanoparticles (SNSC-MNPs) cascade for rapid and efficient DNA digestion. The SNSC-MNPs cascade can fully digest genomic DNA into mono-nucleosides within 30 min. The SNSC-MNPs cascade coupled with HPLC-MS/MS method can accurately and sensitively detect 5-hydroxymethylcytosine (5hmC) changes in genome of human bladder cancer T24 cells induced by tetrachlorobenzoquinone. The immobilization of enzymes on MNPs can enhance the stability and enzymatic activity of the three enzymes, which guarantees the reusability and longtime preservation of the cascades. The relative digestive efficiencies are among 86% -106% up to ten times of reuse. The newly synthesized SNSC-MNPs cascade coupled with HPLC-MS/MS method is promising for fast identification and analysis of structural modifications in genomic DNA.	bladder
Multiorientation Simultaneous Computation of Back-Projection CT Image Reconstruction Algorithm in Staging Diagnosis of Bladder Cancer.	The objective of this research was to investigate the multidirectional synchronous calculation of the back-projection computed tomography (CT) image reconstruction algorithm (MSBP) in the staging diagnosis of bladder cancer. Sixty patients with bladder cancer admitted to the hospital were selected for enhanced CT scanning, all of which were randomly divided into control group (n = 30) and study group (n = 30). The filtered back-projection (FBP) algorithm was employed to reconstruct the scanned image, and the MSBP was additionally applied to the images of the study group. Fringe artifact (SA), overall mass (OQ), effective radiation dose (ED), CT dose-exponential volume (CTDI), and dose-length product (DLP) of the two groups of images were compared and analyzed. The results showed that the total time of the traditional algorithm was 5.473 s, and the total time of MSBP combined with FBP algorithm was 2.832 s, which was significantly higher than that of the traditional algorithm (P < 0.05). CT scan bladder cancer staging results of all patients were compared with surgical pathological staging results, and the results were evaluated according to the coincidence rate. SA in the study group was lower than that in the control group (P < 0.05), and OQ was not statistically significant. The ED of the study group was significantly lower than that of the control group by 33%. The coincidence rate of postoperative pathological staging results and CT staging results was 96%, and T1, T2a, and T4 coincidence rate was 100%, The coincidence rates of T2b, T3a, and T3b were 90%, 83.3%, and 66.67%, respectively. In summary, using MSBP method combined with FBP algorithm can improve OQ while reducing ED of patients. The introduction of MSBP into CT reconstruction image simplified the pixel location operation of projection calculation, showing an important application value in preoperative staging diagnosis of bladder cancer.	bladder
PODNL1 promotes cell migration and regulates the epithelial/mesenchymal transition process in bladder cancer.	PODNL1, a member of the small leucine-rich proteoglycans family, has been identified to be closely associated with the prognosis of ovarian cancer and glioma. In this study, we explored the role of PODNL1 in the progression of bladder cancer (BLCA). TCGA data analysis showed that the expression level of PODNL1 in BLCA tissues was significantly higher than that in adjacent tissues. The high expression of PODNL1 was related to T stage, N stage, pathological stage, pathological grade and histological type of BLCA. The results of qPCR further confirmed that the expression of PODNL1 in BLCA cell lines was significantly higher than that in normal bladder epithelial cells (SV-HUC-1). In addition, PODNL1 knockdown decreased the proliferation and migration abilities of BLCA cells, while PODNL1 overexpression promoted the proliferation and migration abilities of BLCA cells. WGCNA and functional enrichment analysis showed that PODNL1 expression was closely related to the epithelial mesenchymal transformation (EMT) pathway of BLCA. Furthermore, GSCA database analysis also showed that high expression of PODNL1 activated the EMT pathway of BLCA. The results of qPCR indicated that PODNL1 gene expression level was negatively correlated with e-cadherin expression, and positively correlated with N-cadherin expression. Thus, these results suggest that PODNL1 regulates EMT process. Additionally, high expression of PODNL1 was closely associated with poor prognosis in BLCA patients. In conclusion, PODNL1 is a potential therapeutic target and prognostic biomarker of BLCA.	bladder